Racemization during peptide coupling with N,N'‐bis(2‐oxo‐3‐oxazolidinyl) phosphinic chloride (BOP‐Cl)
- 1 April 1987
- journal article
- Published by Wiley in International Journal of Peptide and Protein Research
- Vol. 29 (4) , 464-471
- https://doi.org/10.1111/j.1399-3011.1987.tb02272.x
Abstract
The extent of racemization under various circumstances is reported for the coupling of the N‐protected model dipeptide Z‐Gly‐Phe to Val‐OMe, mediated by N,N'‐bis(2‐oxo‐3‐oxazolidinyl)phosphinic chloride (BOC‐Cl). BOP‐Cl can be used for peptide syntheses either in a one‐pot reaction or with preactivation. Maximum yields are obtained with 1.2 equiv. BOP‐Cl and 1.2–1.5 equiv. amino‐nucleophile and 2.2 equiv. mediatorial base in tetrahydrofuran, but the amount of stereomutation is only tolerable with the use of suppressors (4–6%). BOP‐Cl/ HOBt (88% yield, 0% racemization) and BOP‐Cl/imidazole (96% yield, 1.6% racemization) are the best choices in apolar solvents and HOBt is to be preferred in DMF (89% yield, 2.4% racemization). Most other additives, HOSu, NP, Pfp, ZnCl2, DMAP, etc., are not good suppressors.Keywords
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